The principal objectives of this project are to identify and synthesize compounds with potential as chemopreventative agents. A secondary objective is to understand the relationship between compounds which are dietary components and their chemopreventative activity on the basis of their chemical structures. These efforts involve synthesis of lead compounds, scale-up syntheses of lead compounds, synthesis of analogs based on biogenetic or SAR reasoning, or conversely, synthesis of analogs in order to establish SARs. Compounds emanating from this Project will be evaluated in a battery of assays. Candidate compounds which emerge as leads from this screen are scaled up to quantities sufficient for in vivo testing. This synthetic program is also driven by biosynthetic considerations with respect to the identity of antitumor compounds in plants as conjugates, the nature of intermediates between the conjugates and aglucons, and their possible further metabolism. In the case of the lead compound brassinin, its origin from glucobrassicin and subsequent biogenetic conversion to cyclobrassinin and spirobrassinin led us to synthesize these two congeners which were both highly active. We will synthesize and test glucobrassicin (indole-methylglucosinolate). This is the precursor of indole-3-carbinol, indole-3-acetonitrile and brassinin. We will determine the activities of these aglucons relative to glucobrassicin itself. Lead compounds showing good biological activity among isolated retinoids are deguelin and tephrosin which will be synthesized in 10 g quantities for in vivo testing. Also analogs of deguelin will be synthesized and tested. Work will be continued on cafestol and kahweol specifically with respect to hydroxylation. Approximately 34 analogs will be synthesized and submitted for testing in this project.